EMA Accepts Application for Trastuzumab Biosimilar

The European Medicines Agency has validated and accepted a marketing authorization application for the trastuzumab biosimilar HD201 (Tuznue), according to the developer Prestige BioPharma.

Lisa S. Park

The European Medicines Agency (EMA) has validated and accepted a marketing authorization application for the trastuzumab (Herceptin) biosimilar HD201 (Tuznue), according to the developer Prestige BioPharma.

The application is based on findings from a phase I study and the phase III TROIKA trial (NCT03013504), both of which demonstrated that HD201 is comparable to reference trastuzumab in terms of clinical response, pharmacokinetics (PK), and safety.1,2

“We are very pleased that the EMA has initiated the review of the HD201 marketing authorization application,” Lisa S. Park, chief executive officer of Prestige BioPharma, stated in a press release. “It is a major step in our endeavor to become a global player focusing on biosimilars and innovative biologics. Our development approach has proven to be highly efficient with regard to trial performance, demonstrating exceptional similarity, and dossier filing.”

If approved by the European Commission, HD201 would have the same indications for trastuzumab, which is for the treatment of adult patients with HER2-overexpressing breast cancer as well as those with HER2-overexpressing metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma.

HD201 would also be approved alongside other currently available trastuzumab biosimilars in Europe, which include CT-P6 (Herzuma; trastuzumab-pkrb), ABP 980 (Kanjinti), SB3 (Ontruzant; trastuzumab-dttb), and PF-05280014 (Trazimera; trastuzumab-qyyp).

In a first-in-human, blinded, single-dose, comparative, PK phase I study, investigators randomized 73 healthy male patients to receive 6 mg/kg of intravenous HD201 or trastuzumab sourced in the European Union (EU-trastuzumab). The primary endpoint was area under the curve (AUC) 0-∞; predefined margins of 0.8 to 1.25 were used for equivalence. Secondary endpoints comprised other PK parameters.

Baseline demographic characteristics were similar between the 2 groups. The median age was 29.5 years old (range, 19-45). Additionally, the 90% confidence intervals for the geometric least squares mean of the AUC0-∞ were included within the 0.8 to 1.25 margins, and all other PK parameters were comparable for both HD201 and EU-trastuzumab.

Results showed that PK equivalence was demonstrated between the biosimilar and EU-trastuzumab. Regarding safety, 61.8% and 82.9% of patients experienced adverse events (AEs) in the HD201 and EU-trastuzumab groups, respectively. The most frequently reported, treatment-related AEs were infusion-related reactions. Moreover, no patients tested positive for antidrug antibodies following a single dose of treatment.

In the double-blind, parallel-group, equivalence, multicenter phase III TROIKA trial, 500 patients with HER2-positive early breast cancer were randomized 1:1 to receive HD201 or EU-trastuzumab. Treatment was administered once every 3 weeks for up to 8 cycles in combination of neoadjuvant docetaxel followed by an anthracycline-containing regimen.

Results showed that HD201 was equivalent in physicochemical and biological properties compared with EU- and US-trastuzumab, and is comparable with the standard HER2-targeted agent in terms of clinical response, safety, and pharmacokinetics. Additional data from this study will be presented at the 2019 ASCO Annual Meeting.

Four trastuzumab biosimilars have been approved in the United States. Most recently, in March 2019, the FDA approved PF-05280014 to treat patients with HER2-overexpressing breast cancer as well as HER2-overexpressing metastatic gastric or GEJ adenocarcinoma. Additional FDA-approved trastuzumab biosimilars include CT-P6, SB3, and MYL-1401O (Ogivri; trastuzumab-dkst).


  1. Pivot X, Deslypere JP, Park LS, et al. A randomized phase I study comparing the pharmacokinetics of HD201, a trastuzumab biosimilar, with European Union-sourced Herceptin. Clin Ther. 2018;40(3):396-405. doi: 10.1016/j.clinthera.2018.01.009.
  2. Hii J, Pivot X, Park LS, et al. HD201: analytical biocomparability and clinical trial progression of trastuzumab. J Clin Oncol. 2019;37 (suppl; abstr e12505).